{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T05:55:24Z","timestamp":1790920524969,"version":"4.1.0"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T00:00:00Z","timestamp":1790899200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Emerging evidence supports the presence of autoantibodies targeting interleukin-1 receptor antagonist (IL-1Ra), a regulator of IL-1 signaling, in adult-onset Still\u2019s disease (AOSD). However, existing data are limited by small cohorts and potential confounding due to prior exposure to IL-1 inhibitors. This study aimed to develop a simple and reproducible indirect ELISA for detecting anti-IL-1Ra antibodies and to assess their frequency and immunological features in IL-1 inhibitor-na\u00efve AOSD patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Serum samples from IL-1 inhibitor-na\u00efve AOSD patients (n=46) and healthy controls (n=26) were analyzed using an indirect ELISA based on recombinant IL-1Ra (anakinra) as antigen. Specificity was confirmed by dot blot. Anti-IL-1Ra IgG were affinity-purified from a high-titer patient and characterized by ELISA and SDS-PAGE. Epitope mapping was performed using phage display peptide libraries, followed by sequence alignment and structural mapping onto native IL-1Ra.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Anti-IL-1Ra antibody levels were significantly higher in AOSD patients than in healthy controls (p=0.003), with a greater proportion showing high titers (p&amp;lt;0.001). Levels did not differ between active and inactive AOSD patients. Purified antibodies displayed specific dose-dependent binding to IL-1Ra. Phage display identified two peptide motifs corresponding to linear epitopes mapped to surface-exposed regions of the native protein, indicating recognition of unmodified IL-1Ra domains.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Anti-IL-1Ra antibodies are detectable in IL-1 inhibitor-na\u00efve AOSD patients using a standardized ELISA. The identification of distinct linear epitopes suggests a heterogeneous autoimmune response targeting IL-1Ra and may support a role for adaptive immunity within the Still\u2019s disease spectrum. Further studies are needed to define their functional and clinical relevance.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1957327","type":"journal-article","created":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T05:35:33Z","timestamp":1790919333000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Autoantibodies against interleukin-1 receptor antagonist in Still\u2019s disease in adult patients, data from a multicenter cohort study"],"prefix":"10.3389","volume":"17","author":[{"given":"Piero","family":"Ruscitti","sequence":"first","affiliation":[{"name":"Department of Biotechnological and Applied Clinical Sciences, University of L\u2019Aquila","place":["L\u2019Aquila, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elvira","family":"Favoino","sequence":"additional","affiliation":[{"name":"Rheumatic and Systemic Autoimmune Diseases Unit, Department of 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Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Letizia Pia","family":"Di Corcia","sequence":"additional","affiliation":[{"name":"Fondazione Policlinico Universitario","place":["Rome, Italy"]},{"name":"Research and Clinical Unit of Immunorheumatology, Department of Medicine and Surgery, Universit\u00e0","place":["Rome, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco Maria","family":"Mariani","sequence":"additional","affiliation":[{"name":"Department of Biotechnological and Applied Clinical Sciences, University of L\u2019Aquila","place":["L\u2019Aquila, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Cipriani","sequence":"additional","affiliation":[{"name":"Department of Biotechnological and Applied Clinical Sciences, University of L\u2019Aquila","place":["L\u2019Aquila, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Giacomelli","sequence":"additional","affiliation":[{"name":"Fondazione Policlinico Universitario","place":["Rome, Italy"]},{"name":"Research and Clinical Unit of Immunorheumatology, Department of Medicine and Surgery, Universit\u00e0","place":["Rome, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Perosa","sequence":"additional","affiliation":[{"name":"Rheumatic and Systemic Autoimmune Diseases Unit, Department of Interdisciplinary Medicine, University of Bari Medical School","place":["Bari, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.jaut.2018.07.018","article-title":"A comprehensive review on adult onset Still's 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